Research during the first year of the grant concentrated on further studies on the effect of gangliosides on interleukin-2-\(IL-2) dependent growth of CT-6 cytotoxic T cells. These studies showed that: (1)\inhibition of CT-6 cell proliferation by gangliosides is dose-dependent; (2)\the ganglioside effect is cytostatic rather than cytotoxic, and lowered uptake of [unreadable]3[unreadable]H-thymidine by gangliosides was reflected in lowered cell numbers; (3)\the inhibition is reversible; and (4)\certain gangliosides, e.g., GM[unreadable]2[unreadable], GD[unreadable]1a[unreadable], and G[unreadable]T[unreadable], are much more potent inhibitors than other gangliosides, e.g., GM[unreadable]1[unreadable] and GM[unreadable]3[unreadable]. The studies indicated that terminal IL-2-dependent T-cell proliferation is a particularly sensitive step in lectin-induced mitogenesis to inhibition by gangliosides and suggested that gangliosides may play a role in the receptor for IL-2 in cytotoxic T cells. As one test of this hypothesis, occasional cultures of CT-6 cells that became unresponsive to IL-2 (CT-6-R[unreadable]-[unreadable] cells) were incubated with gangliosides in the presence and absence of IL-2. While gangliosides alone had no effect on CT-6-R[unreadable]-[unreadable] proliferation, IL-2 plus the gangliosides GD[unreadable]1a[unreadable], G[unreadable]T[unreadable] or GM[unreadable]1[unreadable] stimulated growth up to 80 times that of no ganglioside controls. Nonacidic glycosphingolipids were ineffective. A CT-6-R[unreadable]-[unreadable] state was induced when CT-6 cells were grown in serum-free medium in the presence of high concentrations of IL-2. CT-6-R[unreadable]-[unreadable] cells proliferated when low concentrations of gangliosides were included in the medium. Similar effects were observed in studies with murine thymocytes. In the presence of suboptimal concentrations of IL-2, low concentrations of gangliosides increased cellular proliferation, whereas, when cell proliferation was optimized with higher levels of IL-2, gangliosides were inhibitory. Gangliosides, therefore, either inhibit or stimulate the proliferation of T cells depending on the capacity of the cells to respond to IL-2. The data implicate a role for gangliosides in a fully functional IL-2 receptor. (LB)